Reduction of gastrointestinal tract colonisation by Campylobacter

Inventors

Mahdavi, Jafar • Ala'Aldeen, Dlawer

Assignees

Akeso Biomedical Inc

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Publication Number

US-10195172-B2

Patent

Publication Date

2019-02-05

Expiration Date


Abstract

Campylobacter are the commonest reported bacterial causes of gastroenteritis in the UK and industrialized worlds. This invention relates to a method of preventing or reducing the colonization of the gastrointestinal tract of an animal with Campylobacter. Accordingly, the present invention provides a method for disinfection of an animal comprising administering to said animal at least one compound that binds to MOMP or FlaA of Campylobacter in an effective amount to reduce the number of Campylobacter present in the gastrointestinal tract of said animal. The present invention also provides a method of preventing or reducing transmission of Campylobacter from one animal to another.

Core Innovation

The invention relates to preventing or reducing gastrointestinal colonization and transmission of Campylobacter by administering compounds that bind Campylobacter adhesins, including MOMP and/or FlaA. The disclosed approach blocks adhesion to host histo-blood group antigens, which reduces Campylobacter adhesion, biofilm formation, and Campylobacter counts.

MOMP is O-glycosylated at Thr268, and a Thr268/Gly substitution reduces BgAg binding and colonization. The described compounds include a complex of tyrosine with Fe III, as well as ferric quinate and histo-blood group antigen mimetics or sugars, which are linked to the adhesin-binding mechanism to inhibit adhesion and biofilm formation.

A target-selection workflow is described using in silico modeling of glycosylated MOMP and identification of amino-acid residues implicated in BgAg binding. The residues specifically described as implicated include Arg352, Lys278, Lys385, Asn258, Leu290, Tyr294, Phe395, Ile337, Arg381, Asp261, and Ser397.

Claims Coverage

The independent claim covers an animal feed composition that includes a complex of tyrosine with Fe III at 34 to 340 μM effective to inhibit biofilm formation by Campylobacter present in an animal gastrointestinal tract or in a meat product. The claim set includes additional inventive features that refine target organisms, animal classes, efficacy thresholds, binding specificity to defined MOMP residues, and kit context.

Tyrosine–Fe(III) complex feed to inhibit Campylobacter biofilm

An animal feed comprising a complex of tyrosine with Fe III in a concentration from 34 to 340 μM effective to inhibit biofilm formation by Campylobacter present in the gastrointestinal tract of an animal or in a meat product.

MOMP residue-targeted binding specificity

The composition is defined such that the complex specifically binds to at least one specified amino acid residue of MOMP (SEQ ID NO:1) chosen from Arg352, Thr268, Lys278, Lys385, Asn258, Leu290, Tyr294, Phe395, Ile337, Arg381, Asp261, or Ser397.

Quantitative reduction of Campylobacter colony-forming units

The composition reduces Campylobacter colony-forming units in the gastrointestinal tract of the animal by at least 50%.

Campylobacter species limitation

The Campylobacter in the composition is either Campylobacter jejuni or Campylobacter coli.

Poultry class selection

The poultry composition includes poultry selected from chicken, geese, turkeys, or ducks.

Kit formulation context

A kit is provided that includes the composition of claim 1 and may optionally include instructions for using the kit.

Overall, the claim coverage centers on an animal feed composition containing a tyrosine–Fe(III) complex at 34 to 340 μM effective to inhibit Campylobacter biofilm, with additional claim refinements for binding specificity to defined MOMP residues, efficacy as a ≥50% reduction in colony-forming units, limitation to Campylobacter jejuni or Campylobacter coli, specification of poultry subtypes, and a kit including the composition.

Stated Advantages

Inhibits biofilm formation by Campylobacter present in the gastrointestinal tract of an animal or in a meat product.

Reduces Campylobacter colony-forming units in the gastrointestinal tract of the animal by at least 50%.

Documented Applications

Animal feed use to inhibit Campylobacter biofilm formation in the gastrointestinal tract of an animal.

Animal feed use to inhibit Campylobacter biofilm formation in a meat product.

Use directed to poultry, with poultry selected from chicken, geese, turkeys, or ducks.

Use as part of a kit that includes the composition and may optionally include instructions for using the kit.

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